The candidate's long-term career goals focus on the epidemiology and molecular evolution of RNA viruses, including the development of vaccines and technologies to monitor virus circulation and evolution in developing countries. Immediate career objectives concern: (a) the study of Venezuelan equine encephalitis virus, a model for understanding the molecular basis of pathogenesis and epidemiology, and (b) the molecular characterization and production of a vaccine and diagnosis reagents for an emerging arenavirus, Guanarito virus, the etiologic agent of Venezuelan hemorrhagic fever, which the candidate co-discovered. The RCDA will allow the candidate to: (1) concentrate fully on developing innovative multidisciplinary approaches in the study of virus evolution and epidemiology, (2) establish a research program oriented towards the detection and characterization of emerging viruses, and (3) acquire research training in new areas of virology, recombinant DNA technology, cell biology and evolutionary biology. This award would make a difference in the candidate's career by freeing her of teaching and administrative duties which presently take up approximately one third of her time. The specific aims of this research project include: (1) determining the genetic relationships of 14 arenaviruses, to pinpoint the probable origin of Guanarito virus, by comparison of short nucleotide sequences, (2) cloning and sequencing the full genome of Guanarito virus, to understand its molecular biology and produce non-hazardous diagnostic reagents and recombinant vaccine, (3) studying the function of host cell ribosomes in the arenavirus virion, especially their role in viral uncoating, and (4) continuing the studies of Venezuelan equine encephalitis molecular evolution, to understand the mechanisms underlying the generation of epizootic virus, and to contribute to the design of recombinant vaccines against this virus.